15-40751472-T-C

Position:

• chr15-40751472-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018145.3(RMDN3):​c.478A>G​(p.Thr160Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RMDN3 NM_018145.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39

Genes affected

RMDN3 (HGNC:25550): (regulator of microtubule dynamics 3) Enables microtubule binding activity. Involved in cellular calcium ion homeostasis. Located in several cellular components, including intercellular bridge; mitochondrial outer membrane; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2705844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN3	NM_018145.3	c.478A>G	p.Thr160Ala	missense_variant	4/13	ENST00000338376.8	NP_060615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMDN3	ENST00000338376.8	c.478A>G	p.Thr160Ala	missense_variant	4/13	1	NM_018145.3	ENSP00000342493	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.478A>G (p.T160A) alteration is located in exon 4 (coding exon 3) of the RMDN3 gene. This alteration results from a A to G substitution at nucleotide position 478, causing the threonine (T) at amino acid position 160 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	.;D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.2	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.039	D;D;.
Polyphen		0.98	D;D;.
Vest4		0.45
MutPred		0.23		Loss of phosphorylation at T160 (P = 0.0179);Loss of phosphorylation at T160 (P = 0.0179);Loss of phosphorylation at T160 (P = 0.0179);
MVP		0.71
MPC		0.62
ClinPred		0.93	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-41043670;